Abstract:

Purpose: Certain physicochemical characteristics of Candesartan Cilexetil (CC) lead to incomplete oral absorption and poor clinical efficacy. This study assessed the prospect of the use of drug-embedded nanospheres to augment the oral bioavailability of CC. Methods: Baseline studies were conducted to measure the solubility of CC in the polymer. Drug encapsulated poly(lactic acid-co-glycolic acid) nanospheres were prepared by emulsion solvent evaporation method. Five different formulations (C1-C5) were prepared for the varying amount of CC (30-50 mg). Evaluation was carried out for nanospheres characters, drug dissolution and release kinetics. Pharmacokinetics parameters were evaluated in rat model. Results: Solubility of drug in polymer was ~20 mg/100 mg of poly(lactic acid-co-glycolic acid). Values of particle size (200-400 nm), zeta potential (~-25 to -27 mV) and polydispersity index (0.17 to 0.21) were optimal for oral absorption. Morphological studies suggest that the prepared nanospheres were spherical in shape with no aggregation. The nanospheres exhibited biphasic release of CC with an initial burst effect (~50% in 4 h), while it was low and incomplete (~54% in 14 h) with pure drug. Furthermore, drug release from nanospheres appeared to indicate a Korsmeyer–Peppas model (r2=0.981), and diffusion of the drug molecules was by anomalous transport (n=0.74). Greater and rapid absorption of CC was observed from the nanospheres with significantly higher Cmax (599.92 ± 139.36 ng/ml; P<0.0005) and AUC0-∞ (~3 folds; P<0.0001) relative to the pure drug (control). Conclusion: These results suggested that CC loaded nanospheres seems to be a suitable alternative to improve the oral bioavailability and could be further assessed for clinical use.

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